The present proposal outlines an approach to study the secondary sequelae of diabetes based on the hypothesis that these sequelae can be explained by post-synthetic modifications of normal proteins in the diabetic animal or human. That post-synthetic reactions do change the structure and function of naturally occurring proteins has been shown with acetylation reactions resulting from aspirin administration, carbamylation reactions resulting from cyanate administration, and glycosylation reactions to form Hemoglobin AIc in diabetes. This latter example provides a model for similar reactions which probably occur in diabetes. Hemoglobin AIc levels also provide a means whereby the degree of carbohydrate control can be correlated with the development of secondary sequelae. Using techniques derived from studies on the red cell, a rigorous approach to the chemical and physiological definition of these reactions will be undertaken using the platelet and the proteins with which it interacts as a target area because of the central role this cell plays in the micro and macro vascular disease associated with diabetes.